Radiofrequency ablation of Barrett's esophagus

Techniques in Gastrointestinal Endoscopy (2010) 12, 100-107

Techniques in GASTROINTESTINAL ENDOSCOPY www.techgiendoscopy.com

Radiofrequency ablation of Barrett’s esophagus David J. Frantz, MD, MS, Evan S. Dellon, MD, MPH, Nicholas J. Shaheen, MD, MPH Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina. KEYWORDS: Barrett’s esophagus; Radiofrequency ablation; Dysplasia

Barrett’s esophagus, a metaplastic change in the esophagus wherein normal squamous epithelium is replaced by specialized columnar epithelium, is a complication of chronic gastroesophageal reflux disease. There is an association between Barrett’s esophagus and esophageal adenocarcinoma. Since 1977, esophageal cancer has increased by more than 500% in the United States. The optimal treatment for dysplastic Barrett’s esophagus is unclear. One method for treating dysplastic Barrett’s esophagus is radiofrequency ablation (RFA). RFA has been shown to effectively induce reversion to neosquamous tissue, and has been demonstrated in a randomized trial to significantly decrease the risk of progression of dysplasia to cancer. Minimal complications have been reported, and the technique can be performed in an outpatient setting. The aim of this article is to outline and discuss the technical aspects of performance of RFA. The basic principles of RFA and the rationale for adapting this technique to the esophagus will be briefly discussed. Next, the equipment and technique will be explained in detail, including suggestions for improved outcomes. Finally, potential complications, follow-up intervals, and expected outcomes will be addressed. © 2010 Elsevier Inc. All rights reserved.

Barrett’s esophagus is defined as the change of normal esophageal squamous epithelium to columnar epithelium containing goblet cells.1 The metaplastic change is associated with gastroesophageal reflux disease (GERD), and approximately 10% of patients with chronic GERD also have Barrett’s esophagus.2,3 Intestinal mucosa is inherently better suited to withstand an acidic environment, and this change may be a protective physiological response to repeated injury.4 The incidence of Barrett’s esophagus has dramatically increased over the past 30 years.5 One of the driving factors behind this increase may be obesity. A concurrent rise in the average body mass index in the United States has been seen during this same period. Obese individuals appear to be at higher risk for GERD and subsequently Barrett’s esophagus.6 Barrett’s esophagus is usually a benign condition. Longitudinal studies show that most cases of Barrett’s esopha-

The authors report no direct financial interests that might pose a conflict of interest in connection with the submitted manuscript. Address reprint requests to Nicholas J. Shaheen, MD, MPH, Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, CB 7080, Chapel Hill, NC 27599-7080. E-mail: nshaheen@ med.unc.edu 1096-2883/10/$-see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.tgie.2010.02.005

gus do not progress beyond nondysplastic intestinal metaplasia or transient low-grade dysplasia.7,8 However, in a subset of patients, further cellular atypia occurs and the cells accumulate more abnormal characteristics and progress through low-grade dysplasia, and then high-grade dysplasia. In patients with high-grade dysplasia, there is an approximate 5%-10% per patient-year risk of developing esophageal adenocarcinoma.9-11 The overall incidence of esophageal cancer in the United States has risen by more than 500% since the 1970s.5 Esophageal cancer remains highly lethal, and there is still only a 5-year survival rate of less than 15%.12 Despite the dramatic increase in esophageal cancer and Barrett’s esophagus, the optimal management therapy has not been clearly defined for dysplastic Barrett’s disease. Currently, 3 recommended treatments exist for Barrett’s esophagus with dysplasia: intensive endoscopic surveillance, mucosal ablation, and esophagectomy. Esophagectomy is associated with extensive morbidity, and the mortality rate is high in some reports.13,14 Intensive endoscopic surveillance is time- and resource-intensive and is subject to sampling error. Ablative therapy is attractive because it offers the potential for complete eradication of the dysplastic mucosa with a relatively safe side-effect profile. There

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are multiple reported endoscopic ablative therapies, including photodynamic therapy, radiofrequency ablation (RFA), multipolar electrocoagulation, argon plasma coagulation, laser therapies, and cryotherapy with multiple cryogens. This article discusses the technical aspects of performing RFA.

Principles of radiofrequency ablation In RFA, an alternating electrical current at a frequency ranging from the 500 kHz to 1 MHz is applied to the tissue by an electrode array. The alternating current induces an electromagnetic field, which causes electrons and other charged ions to rapidly oscillate. The oscillating molecules collide with one another, and this molecular friction results in a rapid rise in heat. This type of heating is termed resistive or ohmic heating.15,16 Many factors influence the dispersion of energy into tissue and the depth of injury. These factors include the power output of the probe, the frequency of the current, the shape of the antenna array, and the time of exposure. One advantageous physical property of resistive heating is that the heat produced by the magnetic field is proportional to the square of the current density and this rapidly declines with distance from the probe. In addition, desiccated tissue has a much higher resistance than normal tissue. Thus, if the system delivers a large amount of energy in a short period, the temperature of the immediately surrounding tissue will rapidly exceed 100°C. At this temperature, the cells lyse and water rapidly boils off. The coagulated lipid and proteins act as an insulator, and the resistance of the circuit rapidly rises to a point at which little further current can flow to deeper tissue. This acts as inherent control, which allows the system to deliver an ablation depth that is surprisingly consistent and very well controlled.15,16

Technique Instruments The HALO360 and HALO90 ablation system is produced by BARˆRX Medical, Inc (Sunnyvale, CA). The HALO360 device is a catheter with a 4 cm cylindrical balloon with a bipolar electrode array on its surface that delivers energy in a circumferential pattern over a 3-cm length (Figure 1). The ablation catheter comes in multiple diameters (18, 22, 25, 28 and 31 mm) because of the variability of native esophageal diameter. The appropriate size is determined by using the HALO360 sizing balloon, which allows the operator to measure the inner diameter of the esophagus before proceeding to ablation. The sizing balloon is automatically controlled ˆ RX Medical, Inc by the HALO360 Energy Generator (BAR (Sunnyvale, CA). In contrast, the HALO90 device is an articulated bipolar electrode array that attaches to the end of an endoscope and focally ablates areas of the esophagus (Figure 2). The HALO90 device delivers a 20-mm length ⫻

Figure 1 (A) HALO360 Device. (B) Esophagus showing intestinal metaplasia preablation with HALO360. (C) Esophagus after ablation with HALO360.

13-mm width burn. The HALO360 sizing balloon, the HALO360 catheter, and the HALO90 array are all powered by the HALO360 Energy Generator. The HALO360 Energy Generator is activated by the operator through a supplied foot pedal. A guidewire is also needed to perform the procedure. We use a Savary spring tipped guidewire to pass the HALO360 ablation catheter or the HALO360 sizing balloon into the esophagus. A plastic cap is needed to débride the coagulated tissue after treatment. The HALO cap is a polyethylene cap that looks like a banding cap, but is much softer. It attaches to the end of the endoscope and facilitates removal of the ablated mucosa under direct visualization after the first pass

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of ablation with the HALO.360 Finally, a spray catheter is needed to wash the mucosa with a 1% solution of N-acetyl cysteine before ablation to remove excess mucus, which would prevent good contact with the mucosa. Tables 1 and 2 list

Table 1

HALO360 equipment list

Endoscope with associated equipment HALO360 energy generator HALO360 sizing balloon HALO360 balloon ablation catheter (appropriate size) HALO cap Damp gauze 1% N-acetyl cysteine solution Spray catheter Savary spring tipped guidewire

the equipment necessary to perform the HALO360 and the HALO90 procedures, respectively.

Patient consideration and preparation There are few contraindications to RFA. Generally, any medical condition that would preclude a patient from undergoing an upper endoscopy is prohibitive. Severe coagulopathy must be reversed before the procedure because of the risk of bleeding. Abnormal mucosal contour can prevent good probe contact. Any significant esophageal stricture or nodular mucosa that would prevent good tissue apposition by the array must be addressed before therapy. Before starting a course of ablation, it is important to ensure that the disease has been appropriately staged. The patient’s esophageal biopsies are reviewed by a dedicated gastrointestinal pathologist. The upper endoscopy should be repeated if there is any concern that the Barrett’s esophagus has not been appropriately sampled. Reclassification of the extent of disease and degree of dysplasia, because of either differences in histologic interpretation between pathologists or sampling error because of a low number of specimens, is common. Subjects with cancer extending beyond the mucosa may not be definitively treated by radiofrequency therapy because of a considerable proportion with concurrent lymphatic spread at the time of initial evaluation. Although the value of the examination is unclear, we perform an endoscopic ultrasound before ablation of high-grade dysplasia to ensure that there are no invasive lesions, lymphadenopathy, or abnormal wall thickening before ablation. All nodular lesions are removed by endoscopic mucosal resection (EMR) and sent for pathology. If after the endoscopic ultrasound, the esophagus is clear of any concerning lesions, the first RFA can be performed that same day. If any lesions are removed by EMR, the patient will wait 6-8

Table 2

Figure 2 (A) HALO90 Device. (B) Esophagus showing intestinal metaplasia preablation with HALO90. (C) Esophagus after ablation with HALO90. (Color version of figure is available online at www.techgiendoscopy.com.)

HALO90 equipment list Endoscope with associated equipment HALO360 energy generator HALO90 ablation device HALO cap Damp gauze 1% N-acetyl cysteine solution Spray catheter

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Radiofrequency Ablation of Barrett’s Esophagus

weeks for the mucosa to heal completely before coming back for ablative therapy.

Preliminary upper endoscopy and measurements The patient is placed in the left lateral decubitus position and prepared as if undergoing a routine upper endoscopy. The first step is to delineate the extent of Barrett’s esophagus. The patient is given a thorough endoscopic examination with both white light and narrow band imaging. Four measurements are taken (Table 3): the top of the intestinal metaplasia (TIM); the most proximal contiguous extent of the Barrett’s (MAX); the most proximal level at which the Barrett’s is circumferential (CIRC); and the top of the gastric folds (TGF). The endoscopist must carefully inspect the esophagus for subtle strictures or luminal irregularities that might be traumatized by the insufflation of the balloon. Two areas that deserve special attention are the interface of the columnar and squamous mucosa (Z line), where changes in luminal diameter and subtle strictures may hide, as well as the site of previous large EMRs, where luminal diameter may be compromised because of previous scarring. If either of these entities is noted, treating them with the circumferential device should be avoided, and instead, they should be treated with the focal device to lessen the chance of a mucosal rent or perforation. The mucosa is then washed with a 1% solution of N-acetyl cysteine to clear the area of excess mucus that would prevent good contact between the array and the mucosa. After the area is washed, the Savary guidewire is passed into the gastric antrum and the endoscope is then removed.

Sizing The HALO360 sizing balloon is attached to the control unit, and the balloon is tested to ensure that there are no leaks. The HALO360 sizing balloon is then introduced over the wire into the body of the esophagus. The sizing balloon is placed 3 cm proximal to the most proximal extent of the Barrett’s esophagus (TIM). Serial measurements are then taken in 1 cm increments, starting proximally and proceeding distally. A technician or nurse records the esophageal diameter, as well as the suggested diameter of the treatment balloon as displayed on the console of the control unit. Sizing is continued until the diameter of the balloon in-

Table 3

Preablation measurements of the esophagus

Measurements

Definition

TIM MAX CIRC

Top of intestinal metaplasia Most proximal contiguous extent of Barrett’s Most proximal level at which Barrett’s is circumferential Top of gastric folds

TGF

Note: All measurements are taken from the incisors and measured in centimeters.

103 creases markedly (usually to 31 mm, the largest recommended balloon diameter), which indicates that the sizing balloon has entered the gastric cardia. The length at which this occurs can be checked against the measured TGF, to ensure relative conformity. If there is a sizable disparity between the previous endoscopic measurements and the top of the stomach as measured by the sizing catheter, or if the recommended sizes of the treatment balloon are highly variable in the distal esophagus, repeat sizing of the esophagus is recommended. After the sizing procedure, the sizing balloon is removed, keeping the guidewire in place. The smallest diameter treatment balloon suggested throughout the sizing procedure is then chosen as the appropriate ablation catheter. Endoscopists should not be overly concerned if they use a treatment balloon 1 or 2 sizes smaller than the largest esophageal diameter recorded, as the treatment is routinely successful with the smaller balloon even in the largest caliber segments of the esophagus.

Ablation with the HALO360 balloon catheter The appropriate HALO360 balloon ablation catheter is attached to the control unit. It is passed over the guidewire and introduced into the esophagus and positioned at the proximal edge of the intestinal metaplasia (TIM). It is left in place and the endoscope is carefully introduced into the esophagus alongside the catheter and positioned above the HALO360 balloon ablation catheter to confirm appropriate placement. The HALO360 balloon ablation catheter is positioned using both the markers on the catheter shaft, as well as direct visualization. The most proximal end of the electrode array should be positioned 1 cm proximal to the upper margin of Barrett’s esophagus. The balloon is automatically inflated using the foot pedal of the control unit. When inflated, the operator triggers the control unit with a second foot pedal, and radiofrequency energy is delivered to the mucosa. The control unit produces a uniform energy density of 12 J/cm2 and a power density 40 W/cm2 in the array. This produces a uniform burn that ablates approximately 700-1000 ␮m deep throughout the 3 cm length of the array. The energy is delivered in less than 1 second, and the digital readout of the console will confirm delivery of energy. The balloon automatically deflates after the energy has been delivered. A circumferential burn is clearly visible. The HALO360 balloon ablation catheter is then advanced to treat the next 3 cm of mucosa. Attention is taken to only minimally overlap the treated region. Segmental treatment is continued until the complete length of intestinal metaplasia is treated. If the length of the Barrett’s is not divisible by 3, treatment of the most distal segment of the Barrett’s will also imply some thermal injury to the high cardia, which is appropriate and well-tolerated. The endoscope and HALO360 balloon ablation catheter are then removed, again leaving the guidewire in place. The balloon is inflated outside the patient and cleansed with damp gauze to remove adherent desiccated tissue.

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Next, the treated area is débrided of coagulum in preparation for a second treatment. To do this, the HALO cap is attached to the tip of the endoscope, and the endoscope reintroduced into the esophagus. The coagulum in the treatment area is easily removed by gently rubbing the edge of the cap against the treated tissue, using frequent saline lavage and minimal pressure from the scope. The area is débrided in a circumferential pattern starting proximally. Some minor oozing can be expected as the dead tissue is removed. After the area has been débrided, the endoscope is removed from the esophagus. The cap is removed and discarded. The treatment balloon and then the endoscope are again inserted into the esophageal body using the guidewire, as was done in the first round of treatment. A second round of ablation is performed in the same manner, being careful to align the balloon to minimize overlap. A second round of débridement is not necessary. The second burn re-treats the area, decreasing the likelihood of a skipped area, and coagulates the tissue which helps to minimize bleeding. After the second treatment, the endoscope, balloon catheter, and guidewire are again removed, and the patient is sent to the recovery area. The patient is discharged with instructions to follow a liquid diet for 24 hours, followed by a soft diet for 1 week. All patients are discharged on twice-daily proton pump inhibitor therapy. They are prescribed 2% viscous lidocaine with instructions to mix it with a liquid antacid in a 1:1 ratio. Patients are told to take approximately 15 mL of this solution every 2-4 hours as needed for pain relief. In addition, they can use acetaminophen for the first few days. Most patients report adequate pain relief using this combination. As a precaution, they are also given a prescription for low-dose narcotics (acetaminophen with codeine) as needed. Antibiotics are not given for the procedure. The patients are instructed to contact their doctor if they experience fever, worsening pain, or evidence of bleeding after discharge. Most patients are back to their normal activities within a few days. The patients are discharged with a repeat endoscopy appointment in 8 weeks after the initial treatment.

HALO90 ablation device Two months after the initial ablation, patients return for a second treatment. Generally, the first treatment removes 70% or more of the intestinal metaplasia. In unusual cases where the initial treatment has not caused a large proportion of the Barrett’s to revert to neosquamous epithelium, consideration can be made of repeating ablation with the HALO360 ablation catheter as described earlier in the text. If such a poor treatment result is encountered, the patient should also be queried as to compliance with acid suppressive therapy, as this finding may be associated with either noncompliance with medication or inadequate acid suppressive therapy. For most patients, the remaining islands of Barrett’s esophagus are treated using the HALO90 ablation device,

which allows multiple focal areas to be treated. The patient is again prepared for an upper endoscopy and positioned in the left lateral decubitus position. A careful endoscopic examination is performed using both white light and narrow band imaging. The islands of Barrett’s that persist after the first treatment are located, and their approximate positions are recorded by the nurse or technician. The endoscope is removed, and the HALO90 ablation device is connected to the control unit and then attached to the end of the scope. It should be positioned onto the scope so that the back of the array appears in the 12 o’clock position on the video monitor. The device is an articulated array measuring 13 ⫻ 20 mm and is thumbnail shaped. It is engineered to pivot on 2 axes so that the device will be in good apposition to the esophageal wall when the tip of the scope is angulated. The device delivers the same energy density as the HALO360 ablation catheter. The esophagus is washed with the N-acetyl cysteine solution, as with the previous procedure. The islands of Barrett’s that were identified during the initial endoscope are again localized. If multiple islands exist, they are generally treated going from proximal to distal. The first area to be treated is identified, and the scope is angulated toward 12 o’clock position until that the HALO90 ablation device is tightly apposed to the mucosal area that is to be treated. The area is visually checked to ensure that the array is in proper position. If it is not, the scope is manipulated until the operator is satisfied with the array’s position and contact with the mucosa. When the array is appropriately positioned, the operator triggers the control unit, and the control unit delivers the appropriate energy to the area. This takes less than 1 second. Without changing position of the array or the endoscope, a second pulse of energy is delivered to the same location within 2 seconds of the first. Tension on the scope is then relaxed and the next area is treated until all areas have been treated with 2 applications. After the operator is satisfied that all the islands have been treated, the desiccated mucosa is débrided. Two options are possible: one is to remove the scope and replace HALO90 ablation device with the HALO cap, and the second is to use the tip of the HALO90 ablation device. The scope is angulated so that just the forward edge of the array is in contact with the mucosa, and then this can be used to gently débride the area. After débridement of the coagulum, the endoscope is removed and adherent coagulum on the electrode array is removed using damp gauze. Desiccated tissue has a tendency to adhere to the array and can act as an insulator, inhibiting the delivery of the appropriate dose of energy to the tissue. The endoscopist may note that the treated tissue becomes less intensely white if coagulum has built up on the array, suggesting incomplete delivery of energy due to insulation. When this occurs, the array should be removed and cleaned. If large areas of tissue are to be treated, the HALO90 may need to be removed multiple times. After the HALO90 device has been removed and cleaned, a second round of 2 applications is performed in identical manner for 4 applications of energy for the session. Additionally, we

Frantz et al Table 4

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Published complications of radiofrequency ablation

Author

Year

No. patients

Average follow-up

Strictures

Perforations

Chest pain

Bleeding

Hospitalizations

Buried glands

Sharma et al21 Pouw et al22 Velanovich23 Shaheen et al17 Eldaif et al24 Vassiliou et al25 Ganz et al26 Gondrie et al27 Fleischer et al18† Hernandez et al28 Sharma et al29 Gondrie et al30 Sharma et al31 Roorda et al32

2009 2009 2009 2009 2009 2009 2008 2008 2008 2008 2008 2008 2007 2007

63 24 66 84 27 25 142 12 70 10 10 11 100 13

24 22 12 12 2 20 12 14 30 12 24 14 12 12

1 (2%) 1 (4%) 4 (6%) 5 (6%) 0 (0%) 2 (8%) 1 (1%) 1 (8%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)

0 (0%) 1 (4%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)

NA 1 (4%) NA 2 (2%) NA 2 (8%) NA NA 12 (17%) NA N/A NA 12 (12%) 3 (23%)

1 (2%) 1 (4%) 0 (0%) 1 (1%) NA 1 (4%) NA 0 (0%) 1 (1%) 0 (0%) 1 (10%) 0 (0%) 1 (1%) 0 (0%)

0 (0%) 0 (0%) 0 (0%) 2 (2%) NA 0 (0%) NA 0 (0%) 0 (0%) 0 (0%) 1 (10%) 0 (0%) 0 (0%) 0 (0%)

0 (0%) 0 (0%) NA * 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (10%)‡ 0 (0%) 0 (0%) 0 (0%) 0 (0%)

mo mo mo mo mo mo mo mo mo mo mo mo mo mo

*See text: 25.2% of all patients had subsquamous intestinal metaplasia before treatment. After treatment, 40.0% controls and 5.1% treatment group had subsquamous metaplasia, indicating that treatment may be protective. †This is the follow-up to the AIM 2 study.20 Seventy patients of the initial 100 were followed up to 2.5 years. No further complications were found. ‡One case was found and successfully treated with repeat ablation.

treat the area of the Z line circumferentially, even in the situation when it appears normal, to decrease the likelihood of residual microscopic intestinal metaplasia.

Follow-up The patients should return for a repeat endoscopy every 6-8 weeks until all the islands of intestinal mucosa have been eradicated. During each subsequent examination, the mucosa should be examined with white light as well as with narrow band imaging to identify any residual metaplasia. Data suggest that approximately 3.5 treatments may be necessary until dysplastic Barrett’s esophagus is completely ablated.17 After the esophagus has been cleared, the patient is followed up at 3-6 month intervals with endoscopic surveillance and biopsies for a year, then yearly thereafter. Surveillance intervals may be altered if intestinal metaplasia returns. Given the low rate of recurrence of Barrett’s in treated patients, the optimal surveillance frequency (or whether there is further value in ongoing surveillance at all) has not yet been determined.18,19

Managing complications Serious adverse events are rare. The most common side effects encountered are chest pain and odynophagia. On an analog scale from 0 to 100, most patients report a pain level in the mid-20s that returns to baseline within a few days.17,20 Other reported side effects include stricture, bleeding, and perforation (Table 4). The reported stricture rate varies from 0% to 8% and is easily managed with endoscopic dilation.5,17,18,20,21,25,26 Longer segments of Barrett’s requiring circumferential ablation have a higher rate of stricture formation.25 There are a few reported cases of bleeding after the procedure. All cases spontaneously stopped or responded to endoscopic therapy. Most cases occurred in

patients on antiplatelet therapy or anticoagulation.17,20,25,29 Complications requiring hospitalization are infrequent. In the larger series, 3 patients were hospitalized for chest pain or coffee ground emesis. All patients were observed for 24 hours and released.17,29 Perforation is a rare complication. There is 1 reported perforation which occurred after EMR, and was successfully treated with clips and a covered stent.22 Buried intestinal metaplasia is a concern with all ablative techniques. The published reports suggested that buried intestinal metaplasia is a relatively rare event after RFA (Table 4). Interestingly, the recent randomized sham controlled study showed that 25.2% of all patients had subsquamous intestinal metaplasia before RFA therapy. Twelve months after treatment, subsquamous intestinal metaplasia occurred in 5.1% of the patients in the ablation group and in 40.0% of those in the control group (P ⬍ 0.001).17 In addition, a recent publication reported that there is no difference in incidence of squamous overgrowth between control and treatment groups who underwent photodynamic therapy.33 Thus, ablative therapy may not increase the incidence of buried glands.

Results RFA is effective for treating both high- and low-grade intestinal dysplasia. The published rate of complete histologic eradication of dysplasia ranges from 71% to 100%. Complete eradication of intestinal metaplasia ranges from 46% to 100% (Table 5). In the randomized sham controlled trial, patients with lowgrade dysplasia achieved complete eradication of dysplasia in 90.5% of the ablation group compared with 22.7% of patients in the control group at 12 months (P ⬍ 0.0001). The patients with high-grade dysplasia showed complete

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Table 5

Published outcomes of radiofrequency ablation

Author al21

Sharma et Pouw et al22 Velanovich23 Shaheen et al17 Eldaif et al24 Vassiliou et al25 Ganz et al26 Gondrie et al27 Fleischer et al18‡ Hernandez et al28 Sharma et al29 Gondrie et al30 Sharma et al31 Roorda et al32

Year

No. patients

Average follow-up

CRIM*

CRD†

2009 2009 2009 2009 2009 2009 2008 2008 2008 2008 2008 2008 2007 2007

63 24 66 84 27 25 142 12 70 10 10 11 100 13

24 22 12 12 2 20 12 14 30 12 24 14 12 12

79% 88% 93% 77% 100% 78.50% 54.3% 100% 98% 70% 90% 100% 70% 46%

89% 95% NA 86% NA NA 80.4% NA NA NA 100% NA NA 71%

mo mo mo mo mo mo mo mo mo mo mo mo mo mo

*CRIM, Complete response of intestinal metaplasia–all biopsies free of intestinal metaplasia. †CRD, Complete response of dysplasia–all biopsies free of dysplasia. ‡This is the follow-up to the AIM 2 study.20 Seventy patients of the initial 100 were followed to up 2.5 years.

eradication of dysplasia in 81% of the patients in the treatment group compared with the 19% of the control group at 12 months (P ⬍ 0.0001).17 With respect to complete eradication of all intestinal metaplasia, this occurred in 77% of the treatment group and 2.3% of controls, by intention to treat analysis.17

Conclusions No consensus exists on the best course of treatment for dysplastic Barrett’s. Three accepted modalities exist: esophagectomy, observation, and endoscopic ablative therapy. Of these 3, esophagectomy is curative, but has a high associated morbidity and some mortality. Observation is the least invasive, but doesn’t offer treatment with the potential to eradicate dysplasia. Ablation is appealing because it offers the chance of eradication of the lesion with less morbidity and mortality than esophagectomy. Multiple methods of ablation exist or are under investigation, and the optimal method of ablation has yet to be determined. RFA of dysplastic Barrett’s esophagus is a promising technique that has proven effective and is well tolerated with few side effects. The technique achieves ⬎90% complete eradication of low-grade dysplasia and ⬎80% in highgrade dysplasia, with complete eradication of all intestinal metaplasia in more than three-quarters of subjects. The technique is well tolerated, and patients report minimal pain and side effects, which make it suitable for an outpatient setting. Few contraindications exist to performing the procedure, and generally, most patients who are acceptable candidates for upper endoscopy will tolerate RFA.

References 1. Spechler SJ: Clinical practice. Barrett’s Esophagus. N Engl J Med 346:836-842, 2002

2. Abrams JA, Fields S, Lightdale CJ, et al: Racial and ethnic disparities in the prevalence of Barrett’s esophagus among patients who undergo upper endoscopy. Clin Gastroenterol Hepatol 6:30-34, 2008 3. Westhoff B, Brotze S, Weston A, et al: The frequency of Barrett’s esophagus in high-risk patients with chronic GERD. Gastrointest Endosc 61:226-231, 2005 4. Jovov B, Van Itallie CM, Shaheen NJ, et al: Claudin-18: A dominant tight junction protein in Barrett’s esophagus and likely contributor to its acid resistance. Am J Physiol Gastrointest Liver Physiol 293: G1106-G1113, 2007 5. Pohl H, Welch HG: The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence. J Natl Cancer Inst 97:142-146, 2005 6. Murray L, Romero Y: Role of obesity in Barrett’s esophagus and cancer. Surg Oncol Clin North Am 18:439-452, 2009 7. Schnell TG, Sontag SJ, Chejfec G, et al: Long-term nonsurgical management of Barrett’s esophagus with high-grade dysplasia. Gastroenterology 120:1607-1619, 2001 8. Sharma P, Falk GW, Weston AP, et al: Dysplasia and cancer in a large multicenter cohort of patients with Barrett’s esophagus. Clin Gastroenterol Hepatol 4:566-572, 2006 9. Overholt BF, Lightdale CJ, Wang KK, et al: Photodynamic therapy with porfimer sodium for ablation of high-grade dysplasia in Barrett’s esophagus: International, partially blinded, randomized phase III trial. Gastrointest Endosc 62:488-498, 2005 10. Rastogi A, Puli S, El-Serag HB, et al: Incidence of esophageal adenocarcinoma in patients with Barrett’s esophagus and high-grade dysplasia: A meta-analysis. Gastrointest Endosc 67:394-398, 2008 11. Reid BJ, Levine DS, Longton G, et al: Predictors of progression to cancer in Barrett’s esophagus: Baseline histology and flow cytometry identify low- and high-risk patient subsets. Am J Gastroenterol 95: 1669-1676, 2000 12. Eloubeidi MA, Mason AC, Desmond RA, et al: Temporal trends (1973-97) in survival of patients with esophageal adenocarcinoma in the United States: A glimmer of hope? Am J Gastroenterol 98:16271633, 2003 13. Williams VA, Watson TJ, Herbella FA, et al: Esophagectomy for high grade dysplasia is safe, curative, and results in good alimentary outcome. J Gastrointest Surg 11:1589-1597, 2007 14. Law S: Esophagectomy without mortality: What can surgeons do? J Gastrointest Surg (in press) 15. Goldberg SN: Radiofrequency tumor ablation: Principles and techniques. Eur J Ultrasound 13:129-147, 2001

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Radiofrequency Ablation of Barrett’s Esophagus

16. Nath S, Haines DE: Biophysics and pathology of catheter energy delivery systems. Prog Cardiovasc Dis 37:185-204, 1995 17. Shaheen NJ, Sharma P, Overholt BF, et al: Radiofrequency ablation in Barrett’s esophagus with dysplasia. N Engl J Med 360:2277-2288, 2009 18. Fleischer DE, Overholt BF, Sharma VK, et al: Endoscopic ablation of Barrett’s esophagus: A multicenter study with 2.5-year follow-up. Gastrointest Endosc 68:867-876, 2008 19. Shaheen NJ, Sharma P, Overholt BF, et al: 213 A randomized, multicenter, sham-controlled trial of radiofrequency ablation (RFA) for subjects with Barrett’s Esophagus (Be) containing dysplasia: Interim results of the Aim Dysplasia Trial. Gastroenterology 134:A-37A37, 2008 20. Sharma VK, Wang KK, Overholt BF, et al: Balloon-based, circumferential, endoscopic radiofrequency ablation of Barrett’s esophagus: 1-year follow-up of 100 patients. Gastrointest Endosc 65:185-195, 2007 21. Sharma VK, Jae Kim H, Das A, et al: Circumferential and focal ablation of Barrett’s esophagus containing dysplasia. Am J Gastroenterol 104:310-317, 2009 22. Pouw RE, Wirths K, Eisendrath P, et al: Efficacy of radiofrequency ablation combined with endoscopic resection for Barrett’s Esophagus with early neoplasia. Clin Gastroenterol Hepatol 8:23-29, 2009 23. Velanovich V: Endoscopic endoluminal radiofrequency ablation of Barrett’s esophagus: Initial results and lessons learned. Surg Endosc 23:2175-80, 2009 24. Eldaif SM, Lin E, Singh KA, et al: Radiofrequency ablation of Barrett’s esophagus: Short-term results. Ann Thorac Surg 87:405-410, 2009

107 25. Vassiliou MC, Von Renteln D, Wiener DC, et al: Treatment of ultralong-segment Barrett’s using focal and balloon-based radiofrequency ablation. Surg Endosc (in press) 26. Ganz RA, Overholt BF, Sharma VK, et al: Circumferential ablation of Barrett’s esophagus that contains high-grade dysplasia: A U.S. Multicenter Registry. Gastrointest Endosc 68:35-40, 2008 27. Gondrie JJ, Pouw RE, Sondermeijer CM, et al: Stepwise circumferential and focal ablation of Barrett’s esophagus with high-grade dysplasia: Results of the first prospective series of 11 patients. Endoscopy 40:359-369, 2008 28. Hernandez JC, Reicher S, Chung D, et al: Pilot series of radiofrequency ablation of Barrett’s esophagus with or without neoplasia. Endoscopy 40:388-392, 2008 29. Sharma VK, Kim HJ, Das A, et al: A prospective pilot trial of ablation of Barrett’s esophagus with low-grade dysplasia using stepwise circumferential and focal ablation (HALO system). Endoscopy 40:380387, 2008 30. Gondrie JJ, Pouw RE, Sondermeijer CM, et al: Effective treatment of early Barrett’s neoplasia with stepwise circumferential and focal ablation using the HALO system. Endoscopy 40:370-379, 2008 31. Sharma P, Wani S, Rastogi A: Endoscopic therapy for high-grade dysplasia in Barrett’s esophagus: Ablate, resect, or both? Gastrointest Endosc 66:469-474, 2007 32. Roorda AK, Marcus SN, Triadafilopoulos G: Early experience with radiofrequency energy ablation therapy for Barrett’s esophagus with and without dysplasia. Dis Esophagus 20:516-522, 2007 33. Bronner MP, Overholt BF, Taylor SL, et al: Squamous overgrowth is not a safety concern for photodynamic therapy for Barrett’s esophagus with high-grade dysplasia. Gastroenterology 136:56-64, 2009